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dc.contributor.author | Rappazzo, C Garrett | |
dc.contributor.author | Hsieh, Ching-Lin | |
dc.contributor.author | Rush, Scott A | |
dc.contributor.author | Esterman, Emma S | |
dc.contributor.author | Delgado-Romero, Teresa | |
dc.contributor.author | Geoghegan, James C | |
dc.contributor.author | Wec, Anna Z | |
dc.contributor.author | Sakharkar, Mrunal | |
dc.contributor.author | Mas-Lloret, Vicente | |
dc.contributor.author | McLellan, Jason S | |
dc.contributor.author | Walker, Laura M | |
dc.date.accessioned | 2023-05-09T11:58:29Z | |
dc.date.available | 2023-05-09T11:58:29Z | |
dc.date.issued | 2022-09-13 | |
dc.identifier.citation | Immunity. 2022 Sep 13;55(9):1710-1724.e8. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/16032 | |
dc.description.abstract | Human metapneumovirus (hMPV) is a leading cause of acute lower respiratory tract infections in high-risk populations, yet there are no vaccines or anti-viral therapies approved for the prevention or treatment of hMPV-associated disease. Here, we used a high-throughput single-cell technology to interrogate memory B cell responses to the hMPV fusion (F) glycoprotein in young adult and elderly donors. Across all donors, the neutralizing antibody response was primarily directed to epitopes expressed on both pre- and post-fusion F conformations. However, we identified rare, highly potent broadly neutralizing antibodies that recognize pre-fusion-specific epitopes and structurally characterized an antibody that targets a site of vulnerability at the pre-fusion F trimer apex. Additionally, monotherapy with neutralizing antibodies targeting three distinct antigenic sites provided robust protection against lower respiratory tract infection in a small animal model. This study provides promising monoclonal antibody candidates for passive immunoprophylaxis and informs the rational design of hMPV vaccine immunogens. | es_ES |
dc.description.sponsorship | We acknowledge the Immune Monitoring and Flow Cytometry Resource (IMFCSR) at the Norris Cotton Cancer Center at Dartmouth supported by NCI Cancer Center Support Grant 5P30CA023108-41. This work was funded in part by Welch Foundation grant number F-0003-19620604. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject.mesh | Antibodies, Neutralizing | es_ES |
dc.subject.mesh | Antibodies, Viral | es_ES |
dc.subject.mesh | Metapneumovirus | es_ES |
dc.subject.mesh | Respiratory Tract Infections | es_ES |
dc.subject.mesh | Aged | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Epitopes | es_ES |
dc.subject.mesh | Glycoproteins | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Viral Fusion Proteins | es_ES |
dc.subject.mesh | Young Adult | es_ES |
dc.title | Potently neutralizing and protective anti-human metapneumovirus antibodies target diverse sites on the fusion glycoprotein | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 35944529 | es_ES |
dc.format.volume | 55 | es_ES |
dc.format.number | 9 | es_ES |
dc.format.page | 1710-1724.e8 | es_ES |
dc.identifier.doi | 10.1016/j.immuni.2022.07.003 | es_ES |
dc.contributor.funder | NIH - National Cancer Institute (NCI) (Estados Unidos) | es_ES |
dc.contributor.funder | Welch Foundation | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1097-4180 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1016/j.immuni.2022.07.003 | es_ES |
dc.identifier.journal | Immunity | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Microbiología | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.rights.accessRights | open access | es_ES |